Inhibition of early Tc-99m-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma(527 views) Del Vecchio S, Zannetti A, Aloj L, Caracò C, Ciarmiello A, Salvatore M
Keywords: 99mtc-Mibi, Apoptosis, Bcl-2, Breast Cancer, Resistance, Glycoprotein P, Methoxy Isobutyl Isonitrile Technetium Tc 99m, Protein Bax, Protein Bcl 2, Bax Protein, Human, Diagnostic Agent, Oncoprotein, Adult, Article, Breast Carcinoma, Cancer Chemotherapy, Cancer Radiotherapy, Cancer Resistance, Cancer Surgery, Cell Proliferation, Clinical Article, Female, Human Tissue, Image Analysis, Labeling Index, Mitochondrial Membrane, Protein Expression, Protein Family, Protein Function, Scintigraphy, Signal Transduction, Tumor Volume, Breast Tumor, Drug Antagonism, Enzyme Immunoassay, Immunohistochemistry, Metabolism, Middle Aged, Paget Nipple Disease, Pathology, Scintiscanning, Transport At The Cellular Level, Bcl-2-Associated X Protein, Biological Transport, Breast Neoplasms, Immunoenzyme Techniques, Proto-Oncogene Proteins, Proto-Oncogene Proteins C-Bcl-2, Technetium Tc 99m Sestamibi,
Affiliations: *** IBB - CNR ***
Inst. of Biostructures and Bioimages, National Research Council (CNR), Naples, Italy
Dept. of Biomorphological Sciences, University Federico II, Naples, Italy
National Cancer Institute, Naples, Italy
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Inhibition of early Tc-99m-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma
Lack of technetium-99m methoxyisobutylisonitrile ((99m) Tc-MIBI) uptake is consistently reported to predict poor response to subsequent chemotherapy in a variety of human malignant tumours. Since (99m) Tc-MIBI accumulates within mitochondria, which also play a central role in apoptosis through the integration of death signals by Bcl-2 family members, we tested whether early (99m) Tc-MIBI uptake is affected by alterations of the apoptotic pathway. Forty-two breast cancer patients were intravenously injected with 740 MBq of (99m) Tc-MIBI and planar images were obtained 10 min post injection with the patients in the prone lateral position. Ten carcinomas failed to accumulate (99m) Tc-MIBI and could not be visualised on scintigraphic images despite being larger than 1. 8 cm (MIBI negative). Thirty-two of the 42 breast carcinomas showed focal uptake of (99m) Tc-MIBI (MIBI positive), and 10 min tumour-to-background ratios (T/B) varied between 1. 14 and 6. 93. The apoptotic index, the rate of proliferation, and the expression of the anti-apoptotic Bcl-2 protein and pro-apoptotic Bax protein were assessed in surgically excised tumours. All MIBI-negative carcinomas showed a dramatic and statistically significant reduction in the apoptotic index as compared with MIBI-positive lesions (mean+/-SD, 0. 14+/-0. 15 vs 1. 28+/-0. 83, P
Inhibition of early Tc-99m-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma
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